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Metabolomic Profiling for Histologically Fibrotic Stage in Chronic Drug-Induced Liver Injury

Authors :
Xian He
Ming-Xi Zhou
Cheng Cheng
Shan-Shan Li
Yuan Gao
Zhi-Tao Ma
Xin-Hua Song
Zhao-Fang Bai
Zheng-Sheng Zou
Xiao-He Xiao
Jia-Bo Wang
Ya-Wen Lu
Source :
Frontiers in Pharmacology, Vol 13 (2022)
Publication Year :
2022
Publisher :
Frontiers Media S.A., 2022.

Abstract

Background and aims: Chronic drug-induced liver injury (DILI) is a rare but under-researched adverse drug reaction–related disease, which is highly likely to progress into liver fibrosis and even cirrhosis. In this study, metabolomics was used to screen out characteristic metabolites related to the histological progression of fibrosis in chronic DILI and analyze the metabolic changes during the development of fibrosis to explain the underlying mechanism.Methods: Chronic DILI patients who underwent liver biopsy were divided into different fibrosis grades. Serum was analyzed by untargeted metabolomics to find serological characteristic metabolite fingerprints. The screened fingerprints were validated by the validation group patients, and the identification ability of fingerprints was compared using FibroScan.Results: A total of 31 metabolites associated with fibrosis and 11 metabolites associated with advanced fibrosis were identified. The validation group confirmed the accuracy of the two metabolite fingerprints [area under the curve (AUC) value 0.753 and 0.944]. In addition, the fingerprints showed the ability to distinguish the grades of fibrosis by comparing using FibroScan. The metabolite fingerprint pathway showed that bile acid synthesis is disturbed while lipid metabolism is extremely active, resulting in an overload of lipid metabolites in the occurrence and development of chronic DILI–associated fibrosis.Conclusions: Our metabolomic analysis reveals the unique metabolomic fingerprints associated with chronic DILI fibrosis, which have potential clinical diagnostic and prognostic significances. The metabolomic fingerprints suggest the disturbance of the lipid metabolites as the most important factor in the development of DILI fibrosis.

Details

Language :
English
ISSN :
16639812
Volume :
13
Database :
Directory of Open Access Journals
Journal :
Frontiers in Pharmacology
Publication Type :
Academic Journal
Accession number :
edsdoj.b5b29f16a52546ab8b36b5da4b105609
Document Type :
article
Full Text :
https://doi.org/10.3389/fphar.2022.896198